Gitelman syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at November 30, 2016
StartDiseasesGitelman syndrome

Gitelman syndrome is a rare disorder of the kidneys. Also referred to as familial hypokalemia-hypomagnesemia, the condition impairs the ability of the kidneys to reabsorb salt, which results in imbalances in electrolytes and fluid concentrations. Gitelman syndrome is closely related to Bartter syndrome and other disorders that affect the small tubules of the kidneys and cause various electrolyte imbalances.

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Definition & Facts

The exact frequency of Gitelman syndrome is difficult to determine; however, it is believed to affect less than 200,000 people in the United States. The condition appears to affect males and females in approximately the same numbers. The electrolytes most often affected by Gitelman syndrome are calcium, potassium, sodium, chloride, and magnesium.

The condition is typically diagnosed during childhood or early adulthood, but the diagnosis can be complicated by the fact that Gitelman syndrome can be difficult to distinguish from similar disorders. The presentation of the disorder can vary widely, even among members of the same family. Some patients remain virtually asymptomatic while others experience chronic symptoms that affect their quality of life. 

Symptoms & Complaints

Muscle aches, muscle cramps, and muscle spasms are among the most common symptoms of Gitelman syndrome. The condition may cause muscle spasms that affect the face and extremities.

Gitelman syndrome may also cause dizziness and generalized fatigue. Acute episodes may be characterized by fever, abdominal pain, vomiting, constipation, and diarrhea.

Severe electrolyte imbalances may also trigger seizures as well as tingling, numbness, and loss of sensation in the face and hands, cardiac arrhythmias, and low blood pressure.

Individuals with Gitelman syndrome may complain of frequent thirst, excessive urination, and a craving for salty foods. Some patients develop chondrocalcinosis in which calcium accumulates in the joints. This can cause the affected joints to become tender, swollen, red, and warm to the touch.

Some individuals with Gitelman syndrome may go on to develop a potentially serious complication known as rhabdomyolysis in which the muscle tissue breaks down and releases toxins into the body. Rhabdomyolysis can cause kidney damage, impaired muscle coordination, blurred vision, and vertigo.

Although Gitelman syndrome typically causes low blood pressure early in life, it can cause abnormally high blood pressure in middle-aged and older adults. Pregnant women may experience extreme potassium wasting during pregnancy and require supplemental magnesium and potassium. 

Causes

Most cases of Gitelman syndrome are the result of a mutation of the SLC12A3 gene. Less frequently, the disorder is caused by a mutation of the CLCNKB gene. These genes produce a protein that helps transport salts through ion channels in the kidneys that regulate the movement of electrolytes. The anomaly prevents sodium and chloride from being reabsorbed resulting in too much salt being excreted through urination.

Other electrolytes, including magnesium, potassium, and calcium, are also affected. The body attempts to compensate by producing other hormones and proteins, which further exacerbates the fluid and electrolyte imbalance in the body and leads to the symptoms characteristic of Gitelman syndrome.

The disorder is autosomal recessive. This means that a person has to inherit two copies of the defective gene in order to be affected. If a person only inherits one copy of the gene, they are considered carriers but do not develop any signs or symptoms of the condition.

If two carriers of Gitelman syndrome have a child, there is a 25 percent chance that the child will have the condition, a 50 percent chance that the child will be a carrier, and a 25 percent chance that the child will be neither affected nor a carrier. 

Diagnosis & Tests

A doctor will diagnose Gitelman syndrome based on a patient’s symptoms, medical history, family history, and a battery of specialized tests to rule out more common causes of electrolyte and metabolic imbalances. Blood tests may be used to measure serum electrolyte and hormone levels. These tests will typically demonstrate low levels of magnesium and elevated levels of aldosterone and renin.

Clinical urine tests can help identify high levels of potassium and sodium and low levels of calcium in the urine. There is a molecular genetic test that can specifically identify genetic mutations responsible for Gitelman syndrome; however, these tests are only available through a limited number of specialized laboratories. 

Treatment & Therapy

There is currently no cure for Gitelman syndrome. Treatment is based on the patient’s individual symptoms and typically involves a team of specialists, including internists, nephrologists, and cardiologists. Individuals who remain asymptomatic do not normally require treatment but should be monitored on a regular basis.

The primary treatment is supplemental potassium and magnesium. Most patients must continue the treatment daily for the rest of their lives. Episodes involving extreme muscle cramps may require intravenous magnesium. Affected individuals may also benefit from taking amiloride or spironolactone. These medications are potassium-sparing diuretics that increase the amount of water excreted in the urine but prevent the loss of potassium.

Pain medications, nonsteroidal anti-inflammatories (NSAID's), and magnesium may help patients experiencing joint pain and inflammation caused by chondrocalcinosis. The nonsteroidal anti-inflammatory drug, indomethacin may help improve growth in children with certain early-onset forms of the disorder.

Individuals with Gitelman syndrome are encouraged to undergo periodic cardiac evaluations to screen for arrhythmias and other cardiac risk factors. Anyone affected by the disorder should eat a high-potassium and high-sodium diet.

Overall, the long-term prognosis for most patients with Gitelman syndrome is good. The disease is not progressive, and complications tend to be most common in patients who do not follow care recommendations. In very rare cases, patients have developed chronic renal insufficiency.

Prevention & Prophylaxis

Gitelman syndrome cannot be prevented since it is an inherited genetic disorders. Individuals with a personal or family history of the condition may want to consult a genetic counselor in order to better understand the risks of passing the condition to their offspring.

Most patients are able to have a normal quality of life by following treatment guidelines aimed at maintaining the proper fluid and electrolyte balance. As a general rule, patients with Gitelman syndrome should avoid competitive sports and other intense physical activities that can induce excessive sweating and cause a loss of potassium and magnesium.